The present application represents the competitive renewal of the Cancer Center Support Grant (CCSG) for The Burnham Institute's Cancer Center. The Cancer Center has been a recipient of CCSG support from the National Cancer Institute since 1981. The Burnham Institute is an independent, non-profit organization dedicated to basic research related to cancer and other degenerative diseases. Since the last competitive renewal of the CCSG, the Institute's Cancer Center membership has increased from 34 investigators to its current total of 54 primary, secondary and adjunct members. In addition, the Institute now contains a smaller Neurosciences and Aging Research Center. However, cancer-related research remains by far the predominant scientific focus of The Burnham Institute. The Cancer Center contains 6 scientific programs: (1) Cell Adhesion and Extracellular Matrix;(2) Glycobiology;(3) Oncodevelopmental Biology;(4) Cancer Genetics and Epigenetics;(5) Signal Transduction Research;and (6) Apoptosis and Cell Death. During the past funding period, the Cancer Center has further enhanced its position of scientific prominence in the areas of cell-matrix interactions, glycobiology and cell death mechanisms. Several new shared resources have been developed (e.g., the High-throughput Cell Analysis Facility), and 11 new, full-time faculty members have been recruited into Cancer Center Programs as primary or secondary members. Developing areas of research strength include mitogenic and stress-induced signal transduction, genome surveillance, and genetic instability. During the next funding period, our overarching plan for Center development is to integrate chemical biology into the existing blend of cell biology and structural biology that characterizes each of our programs. Our goals are to encourage the use of small molecules as probes for studies of normal and cancer cell biology, and to develop lead compounds that might serve as candidates for further development as anticancer drugs. To accomplish these objectives, the Cancer Center will facilitate research activities related to chemical library screening, high-throughput cell analysis, gene microarray analysis, and proteomics. In addition, we plan to build additional expertise in chemistry and chemical biology through the recruitment of new faculty into the Center. Our overall objective is to forge more direct connections between our discovery-based research and the development of novel strategies for cancer prevention and therapy.